Core B will breed and genotype CF mouse models including cftr and congenic derivatives thereof, CftrtmicAM> CftrG55iD] (^117^ gs we|| as FABP_numan CFTR+A transgenic (Tg) mice on a Cftr ^ background. The Core will also propagate a p11 knock-out mouse intended for studies of CFTR membrane recycling, and help P30 investigators test the influence of defective TGF-/? signaling on the CF phenotype using a TGF receptor-defective mouse characterized at our institution. New CF mice will be generated in the Core, including 'knock in' mouse models encoding prematurely truncated CFTR (Class I mutations). In addition, Tg(Scgb1a1-Scnn1b), a murine model exhibiting a CF-like pulmonary phenotype, will be provided to P30 investigators for projects such as those to investigate new mediators of inflammation in CF lung disease. Core B will also conduct testing with novel flexiVent equipment for assessing murine lung function. This system measures resistance, elastance, and compliance (and performs pressure-volume loop measurements of murine lungs), and can aerosolize compounds while simultaneously recording lung function in real-time. Like other laboratories, we have found that this sensitive equipment can discriminate CF from non-CF mice. The capabilities will allow us to evaluate new inflammatory pathways (HMGB1 and PGP) in CF airways. Preclinical assessment of CF therapies (PTC124) can be accomplished in the same way. Core B is experienced with bioelectric methods necessary to track changes in CFTR activity in vivo or ex vivo (transepithelial potential difference, short circuit current) and will provide these to P30 investigators who require the measurements for their CF research programs. In summary, Core B will provide mouse models and conduct state-of-the art assays necessary to examine CF disease mechanism in vivo, and facilitate preclinical evaluation of experimental therapeutics for the disease.